EULAR: RA Response Abides After TNF Drug Stopped

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Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Note that this study suggests that patients who respond to a combination of the TNF inhibitor and methotrexate are likely to maintain the response with cessation of the biologic after 26 weeks of therapy.

LONDON -- Patients with early, active rheumatoid arthritis who achieve low-disease activity after treatment with adalimumab (Humira) plus methotrexate were able to stop taking the biologic and maintain disease control on methotrexate alone, researchers reported here.

In a multicenter, randomized trial, among the patients classified as responders to the combination therapy after 26 weeks of treatment, 94% of those on monotherapy continued to have an ACR20 response for an additional year, according to Paul Emery, MD, from the University of Leeds, in Leeds, England, and colleagues. The ACR response is the American College of Rheumatology criteria for clinical improvement of symptoms.

Similarly, 95% of those who continued with both methotrexate and the tumor necrosis factor (TNF) inhibitor maintained an ACR20 response at week 72 (P=0.72), the investigators reported here at the annual meeting of the European League Against Rheumatism (EULAR).

"This is very important from a cost-effectiveness point of view, and in the U.K., we have been trying to achieve remission induction with biologics, and then maintenance with disease-modifying drugs such as methotrexate," Emery said in a EULAR press conference.

"This is one of the first, big randomized studies where patients were able to stay controlled after withdrawal of the biologic," he told MedPage Today.

The study included 1,032 patients with RA of less than one year's duration, whose disease activity score in 28 joints (DAS28) was 3.2 or higher.

For inclusion, patients' erythrocyte sedimentation rate had to be elevated to 28 mm/h or more. C-reactive protein had to be at least 1.5 mg/dL.

In addition, enrolled patients had more than one joint erosion, and were positive either for rheumatoid factor or anti-cyclic citrullinated peptide.

At baseline, the mean duration of RA was about four months, the mean DAS28 was 5.8, and C-reactive protein was 25 mg/L.

The mean number of joints affected was 24, and the mean number of swollen joints was 16.

Mean total Sharp score, which assesses joint damage and erosions, was 11.

"These patients had severe disease," said Emery, who is currently the president of EULAR.

During the first 26 weeks, patients received adalimumab (40 mg every other week) or placebo plus methotrexate.

The 44% who responded at week 26 were then randomized again to continue adalimumab plus methotrexate or to methotrexate alone.

Through week 78, patients in both groups continued to do well, although the patients continuing on adalimumab did better on more stringent criteria of disease response:

ACR50: 89% versus 80% (P=0.11)

ACR70: 77% versus 65% (P=0.05)

DAS28 <3.2 (low disease activity): 91% versus 81% (P=0.04)

DAS28 ≤2.6 (remission): 86% versus 66% (P=0.001)

Total Sharp score ≤0.5: 89% versus 81% (P=0.06)

The results of this study confirm that early treatment of RA with adalimumab can achieve high levels of disease control.

"Importantly, results of this first global study assessing biologic-free disease control demonstrate that it may be possible to successfully withdraw anti-TNF therapy in certain patients and maintain long-term positive outcomes," Emery said.

He also explained that he and his co-investigators tried other induction time periods before settling on 26 weeks. They found, for instance, that three months was not long enough, although three months might be adequate for patients with milder disease, he said.

Further studies are needed to confirm long-term outcomes and to identify those patients most likely to succeed with biologic-free control of their RA.

To that end, the investigators are now reanalyzing the data to look at 78-week outcomes in patients who achieved remission, rather than just low disease activity, at week 26.

Emery and several co-investigators reported receiving research support and consulting for several pharmaceutical companies, including Abbott, BMS, Roche, Centocor, and Merck.

Several also are employees of Abbott or are shareholders in the company.

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